Rare copy number variation in autoimmune Addison’s disease

• DOI: 10.3389/fimmu.2024.1374499
• Publication Date: 2024-03-18T05:00:06Z
• Authors: Haydee Artaza; Daniel Eriksson; Ksenia Lavrichenko; Maribel Aranda-Gu...; Eirik Bratland; Marc Vaudel; Per Knappskog; Eystein S. Husebye; Sophie Bensing; Anette S. B. Wolff; Olle Kämpe; Ellen C. Røyrvik; Stefan Johansson
• Keywords: Genome-wide Association Study

Autoimmune Addison’s disease (AAD) is a rare but life-threatening endocrine disorder caused by an autoimmune destruction of the adrenal cortex. A previous genome-wide association study (GWAS) has shown that common variants near immune-related genes, which mostly encode proteins participating in immune response, affect risk developing this condition. However, little known about contribution copy number variations (CNVs) to AAD susceptibility. We used genotyping data from Norwegian and Swedish individuals (1,182 cases 3,810 controls) investigate putative role CNVs aetiology. Although frequency was similar between controls, we observed larger deletions (>1,000 kb) were more among patients (OR = 4.23, 95% CI 1.85-9.66, p 0.0002). Despite this, none large case-deletions conclusively pathogenic, clinical presentation AAD-polygenic score with without CNVs. Among exclusive AAD, highlight two ultra-rare genes LRBA BCL2L11 , speculate might have contributed polygenic these carriers. In conclusion, do not appear be major cause further studies are needed ascertain potential load